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Study on the Specialized Function of Dendritic Cells

Research Project

Project/Area Number 08044271
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research Field Immunology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

INABA Kayo  KYOTO UNIVERSITY Graduated School of Science, Associated Professor, 大学院理学研究科, 助教授 (00115792)

Co-Investigator(Kenkyū-buntansha) AUSTYN Jonathan M  University of Oxford, Naffield Department of Surgery, Lecturer, ナフィールド外科部門, 講師
STEINMAN Ralph M  The Rocefeller University, Professor, 細胞生理免疫学部門, 教授
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 1997: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1996: ¥3,500,000 (Direct Cost: ¥3,500,000)
Keywordsdendritic cells / antigen-presentation / antigen processing / MHC class II / immune response / cell differentiation / cell interaction / 機能的成熟
Research Abstract

Dendritic cells (DC) are distinctive leukocytes that are specialized antigen-presenting cells for T cell mediated immune responses. They acquire antigens in peripheral tissues and migrate to T area of lymphoid organs where they present processed peptides in context of MHC class II to T cells. In normal steady state, 2-3 distinguishable subpopulations of DC in respect of phenotype and function have been reported to locate in lymphoid organs, and it is suggested they may be different not only in maturational steps but also in developmental pathways from precursors. Therefore, we attempted to isolate T area DCs from lymph nodes and characterize phenotype and antigen-presenting and costimulatory functions. We also investigated the features of development and functional maturation of DCs in vivo and in vitro, and antigen-presenting activity after inoculating DNA encoding antigenic determinant recognized by CD4 T cells. The results obtained are 1) T area DCs present high levels of self peptides in addition to MHC class II and various adhesion and costimulatory molecules and induce apoptosis of specific T-T hybridomas, suggesting they regulate self reactivity in the periphery ; 2) Immature early-stage of DCs in which most class II are intracellular and localized to lysosomes, undergo maturation to become highly stimulatory through the intermediate stage, in which intracellular class II are found in peripheral non-lysosomal vesicles. The decrease in rate of class II degradation and increase in expression of surface class II is a fundamental feature of DCs maturation and is also exhibited by a very different population of DC ; 3) DCs isolated either from draining lymph nodes or skin present antigens to T cells and carry plasmid DNA,indicating that the uptake of DNA and/or the protein expressed by DCs triggers immune responses to DNA vaccines.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Yamaguchi,Y.: "Contrasting effect of TGFβ1 and TNFα on the development of dendritic cells from progenitors in mouse bone marrow." Stem Cells. 15. 144-153 (197)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Doi,H.: "Pluripotent hemopoietic stem cells are c-kit^<<low>." Proc.Natl.Acad.Sci.USA. 94. 2513-2517 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Inaba,K.: "Dendritic cells as antigen presenting cells in vivo." Immunol.Cell Biol.75. 206-208 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mori,S.: "Presence of B cell progenitors in the thymus." J.Immunol.158. 4193-4199 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Pierre,P.: "Developmental regulation of MHC class II transport and compartmentalization in mouse dendritic cells." Nature. 388. 787-792 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Steinman,R.M.: "Dendritic cell development and maturation." Adv.Exp.Med.Biol.417. 1-6 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Steinman,R.: "Dendritic cells in the T cell areas of lymphoid organs." Immunol.Rev.158. 193-199 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Inaba,K.: "High levels of an MHC class II-self peptide complex on dendritic cells from the T cell areas of lymph nodes." J.Exp.Med.186. 665-672 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Casares,S.: "Antigen presentation by dendritic cells following immunization with DNA encoding a class II-restricted viral epitope." J.Exp.Med.186. 1481-1486 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamaguchi, Y., Tumura, H., Miwa, M.and Inaba, K.: "Contrasting effect of TGFbeta1 and TNFalpha on the development of dendritic cells from progenitors in mouse bone marrow." Stem Cells. 15. 144-153 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Doi, H., Inaba, M., Yamamoto, Y., Taketani, S., Mori, S.-I., Sugiura, A., Ogata, H., Toki, J., Hisha H., Inaba, K., Sogo, S., Adachi, M., Matsuda, T., Good, R.A.and Ikehara, S.: "Pluripotent hemopoietic stem cells are c-kit^<<low.>" Proc.Natl.Acad.Sci.USA. 94. 2513-2517 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Inaba, K.: "Dendritic cells as antigen presenting cells in vivo." Immunol.Cell Biol.75. 206-208 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mori, S,Inaba, M., Sugiura, A., Taketani, S., Doi, H., Fukuba, Y., Yamamoto, Y., Adachi, Y., Inaba, K., Fukuhara, S.and Ikehara, S.: "Presence of B cell progenitors in the thymus." J.Immunol.158. 4193-4199 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Steinman, R.M., Pack, M.and Inaba, K.: "Dendritic cells in the T cell areas of lymphoid organs." Immunol.Rev.158. 193-199 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Pierre, P., Turley, S.J., Gatti, E., Webster, P., Hull, M., Meltzer, J., Mirza, A., Inaba, K., Steinman, R.M.and Mellman, I.: "Developmental regulation of MHC class II transport and compartmentalization in mouse dendritic cells." Nature. 388. 787-792 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Steinman, R.M., Pack, M.and Inaba, K.: "Dendritic cell development and maturation." Adv.Exp.Med.Biol.417. 1-6 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Inaba, K., Pack, M., Inaba, M., Sakuta, H., Isdell, F.and Steinman, R.M.: "High levels of an MHC class II-self peptide complex on dendritic cells from the T cell areas of lymph nodes." J.Exp.Med.186. 665-672 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Casares, S., Inaba, K., Brumeanu, T.-D., Steinman, R.M.and Bona, C.A.: "Antigen presentation by dendritic cells following immunization with DNA encoding a class II-restricted viral epitope." J.Exp.Med.186. 1481-1486 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamaguchi, Y.: "Contrasting effect of TGFβ1 and TNFa on the development of dendritic cells form progenitors in mouse bone marrow." Stem cells. 15. 144-153 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Doi, H.: "Pluripotent hemopoietic stem cells are c-kit^<<low>." Proc.Natl.Acad.Sci.USA. 94. 2513-2517 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Inaba, K.: "Dendritic cells as antigen presenting cells in vivo." Immunol.Cell Biol.,. 75. 206-208 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mori, S,: "Presence of B cell progenitors in the thymus." J.Immunol.158. 4193-4199 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Pierre, P.: "Developmental regulation of MHC class II transport and compartmentalization in mouse dendritic cells." Nature. 388. 787-792 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Steinman, R.M.: "Dendritic cell development and maturation." Adv.Exp.Med.Biol.417. 1-6 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Steinman, R: "Dendritic cells in the T cell areas of lymphoid organs." Immunol.Rev.158. 193-199 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Inaba, K.: "High levels of an MHC class II-self peptide complex on dendritic cells from the T cell areas of lymph nodes." J.Exp.Med.186. 665-672 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Casares, S.: "Antigen presentation by dendritic cells following immunization with DNA encoding a class II-restricted viral epitope." J.Exp.Med.186. 1481-1486 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Young,J.W.: "Dendritic cells as adjuvants for class I restricted anti-tumor immunity." J.Exp.Med.183. 7-11 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Frazle Akber: "Upregulation of MHC class II antigen on dendritic cells from hepatitis B virus transgenic mice by γ-interferon:abrogation of immune response defect to a T-cell-dependent antigens" Immunology. 87. 519-527 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ortner,U.: "An improved method to obtain murine migratory cutaneous dendritic cells." J.Immunol.Methods. 193. 71-79 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Inaba,K.: "Dendritic cells as antigen presenting cells in vivo." Immunol.Cell.Biol.(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamaguchi,Y.: "Contrasting effect of TGFβ1 and TNFα onthe development of dendritic cells from progenitors in mouse bone marrow." Stem Cells. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Steinman,R.M.: "Dendritic cells in the T cell areas of Iymphoid organs" Immunol.Rev.(in press). (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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